1. Field of the Invention
The present invention relates generally to sterilization carried out in a blow fill seal machine. In particular, the invention is directed to an automated sterilization process for the product pathway of a blow fill seal machine.
2. Description of the Related Technology
Blow-fill-seal (BFS) machines combine a process of antiseptically blow-molding hollow containers with an aseptic process of filling and sealing the containers, all in one machine cycle. By eliminating individual machines for separately blow-molding the container, filling the container, and sealing the filled container, the BFS machine delivers significant savings in space and efficiency while maintaining a medically sterile environment within the machines for the aseptic production process. Using the BFS technology, a container is formed, filled, and sealed in a continuous flow without human intervention, in a sterile enclosed area inside a machine, which ensures that the packaged product is free of contamination.
Over the last 20 years, BFS technology has become particularly prevalent within the pharmaceutical industry. It is now widely considered to be the superior form of aseptic processing technology for packaging of pharmaceutical and healthcare products by various regulatory agencies including the U.S. Food and Drug Administration (FDA).
The FDA emphasizes on product safety and requires manufacturers to ensure aseptic processing of all pharmaceuticals. It is thus critical to maintain a fully sterile environment within BFS machines, especially their product pathways. In a typical pharmaceutical packaging process, bulk pharmaceutical (solutions or liquids) prepared under low bio-burden or sterile conditions are delivered to the BFS machine in a sterile bulk holding tank, from which the pharmaceutical is delivered via a product pathway to a filling nozzle to be injected into formed containers.
Many processes for sterilizing BFS machines and/or their product pathways have been developed with various degrees of success. US 2011/0146202 discloses a process for maintaining a sterilization state in a mold-fill-seal machine. The internal space and outer surfaces of internal components of the machine are sterilized with a chemical liquid. Further, a positive-pressure environment is maintained within the machine with filtered clean air, which improves the aseptic level of packaged products. The outer surfaces of the machine may be sterilized with a chemical agent or heat-sterilized with aseptic water at high temperature. These treatments may be adjusted by consideration of the frequency of sterilization and the degree of contamination of the machine.
GB 1 201 069 discloses a process using steam to sterilize a BFS machine. The steam passes through pipes into a filling tank of the machine to sterilize the filling tank. The steam is used only for initial sterilization of the machine and is not suitable for sterilization of the BFS machine once its filling tank has been loaded with a product or when the BFS machine is in production mode.
U.S. Pat. No. 4,790,117 discloses a method of sterilizing the internal parts of a BFS machine by charging the machine with a sterilizing agent such as super-heated steam, a disinfection liquid, sterilizing gas, or the like for initial and continuous sterilization of the machine.
U.S. Pat. No. 6,298,638 discloses a process for maintaining sterility in a BFS machine during filling and minimizing the oxygen uptake of product being filled. The process requires placing the filling nozzle discharge port at a location that does not break a sterile fill plane which passes across the upper end of containers. This contributes to reducing the chance of contamination inside the containers.
Forcinio, “BFS equipment streamlines the package process,” Pharmaceutical Technology, vol. 34, pp. 38-46, (2010) discloses the general concept of using steam to sterilize a product pathway in a BFS machine by an automated process. However, neither the critical process parameters nor other necessary details of the process are taught in the article.
The present invention provides a fully automated process and system for sterilizing a product pathway of a BFS machine that eliminates human manual intervention once the process has been initiated. Since human intervention may introduce errors and is a potential source of contamination to the BFS machine, the present process is a more reliable sterilization process.